Alan Dwi Setiawan

01071200089

LO & WO Cardio Week 3 - Jumat

1. Interpretasi ECG pada kasus week 1 dan 2.

Week 1

 Identitas : Bukan identitas dari Ms. Humaeroh

 Kalibrasi : kecepatan = 25mm/sec
: Voltase = 10 mm/mV
 Rythm : Sinus Rythm
 Heart Rate : Reguler  300/5 = 60 bpm (normal)
 Axis : Deviasi ke Right Axis
 P Wave Morphology : Normal
 T wave : Normal, Not inverted
 ST Segment : Flat
 QT Interval : Half PR interval

deviate to right axis, with incomplete right bundle branch block. This is a typical finding in
patients with ASD
Week 2

 Identitas : Tidak terlihat identitas Mr. Damar

 Kalibrasi : kecepatan = 25mm/sec
: Voltase = 10 mm/mV
 Rythm : Sinus Rythm
 Heart Rate : Reguler  300/5 = 60 bpm (normal)
 Axis : Normal
 P Wave Morphology : P mitrale
 T wave : Normal, Not inverted
 ST Segment : ada depression
 QT Interval : Half PR interval

“P mitrale” is a sign of left atrium enlargement.

2. Describe and practice the recording and interpretation of electrocardiogram.

EKG Interpretation

Before you read the EKG, look for:

 Patient age: as many values change with age

 Standardization: full standard is two large squares (1 mV, 10 mm) and half standard is
one large square (0.5mV, 5 mm)
 Paper speed: the standard is 25 mm/sec, the faster the paper speed the slower the HR
will look and vice versa
Basic EKG interpretation

1. Heart rate: The standard paper speed is 25 mm (5 large squares)/sec. This means that if
the interval between two beats (R-R) is 5 large squares, the HR is 60 beat/min.

 The HR may be counted by simply dividing 300 by the number of the large squares
between two heart beats (R-R).
 If the interval between two beats is one large square, the HR is 300 beat/min, 2
squares →150, 3 squares →100, 4 squares → 75, 5 squares → 60, 6 squares → 50
beat/min.

Fi
gure 1: Calculating heart rate on EKG sheet, HR ~ 120
2. Rhythm: The cardiac myocytes have an inherent automaticity and can generate an electric
impulse. The SA nodal cells have the fastest automaticity (pacemaker) and hence control the
heart rate and rhythm. There are 4 levels of conductions and potential pacemakers in the heart
from fastest to slowest: SA node → atria → AV node → ventricles. If the rhythm is not sinus,
we have to determine the origin of the pacemaker and where the impulse is initiated.

 SA nodal rhythm (normal sinus rhythm) (NSR) (Figure 2)

1. The sinus node is located at the SVC/right atrial junction. Sinus rhythm requires ALL
of the following 3 criteria:
1. One P wave preceding each QRS complex
2. All P waves should be uniform in shape
3. Normal P wave axis is in the left lower quadrant (0-90 degrees), i.e. upright in
both lead I and aVF (unless there is dextrocardia)
2. The R-R interval in NSR does not have to be identical as it may change with
breathing (sinus arrhythmia) (Figure 3.) The sinus arrhythmia is easier to appreciate
with slower heart rates.
1. HR increases during inspiration due to:
 Increased venous return
 Increased sympathetic tone
2. HR decreases during expiration due to:
 Decreased venous return
 Increased parasympathetic tone

 Atrial rhythm (Figure 4)

 1. Characterized by narrow QRS complexes preceded by P waves that do not fulfill one
or more of the normal sinus rhythm (NSR) criteria mentioned earlier.
2. If the P wave morphology changes, this may indicate a multifocal origin which is
called "wandering pacemaker".

 AV nodal or junctional rhythm (Figure 5)

1. Characterized by narrow QRS complexes that are not preceded by P waves.

2. An inverted P wave may be seen following the QRS due to retrograde conduction.

 Ventricular rhythm (Fgure 6)

1. Characterized by wide QRS complexes that are not preceded by P waves.

If the sinus node fails to initiate the impulse, an atrial focus will take over as the pacemaker,
which is usually slower than the NSR. When the atrial focus fails, the AV node will take
over. Subsequently, if the AV node fails, the ventricular focus, which is the slowest, will take
over as a pacemaker. Each time the focus is downgraded, the heart rate becomes slower based
on the inherent automaticity of the pacemaker.

Fig
ure 2: Diagnosis:Normal Sinus Rythm
 
3. Axis: Determine both P wave and QRS axes. The net summation of positive and negative
deflection is used to determine the axis. Look for two perpendicular leads (usually lead I and
aVF) to determine in which quadrant the axis is located.

a) If QRS is positive in lead I and positive in aVF, the axis is in the left lower
quadrant (0-90 degrees), which is normal
b) If QRS is negative in lead I and positive in aVF, the axis is in the right lower
quadrant (90-180 degrees). This represents right axis deviation which can be
normal in children.
c) If QRS is positive in lead I and negative in lead aVF, the axis is in the left
upper quadrant (-90- 0). This represents left axis deviation.

d. If QRS is negative in lead I and negative in lead aVF, the axis is called

indeterminate. Precordial leads may determine if it is an extreme right or left
axis deviation.

4. Durations/Intervals:
a) P wave: Represents atrial depolarization. Normally it is 2.5 mm wide and 2.5 mm high.

 Tall P waves = right atrial enlargement (RAE)

 Wide P waves = left atrial enlargement (LAE)
 Wide and tall or bi-peaked P waves = bi-atrial enlargement (BAE).
b) PR interval represents a delay in conduction in the AV node. It varies with age and heart
rate and is usually <0.2 sec at any age.

c) QRS duration: Represents ventricular depolarization. Normally 2 small squares or 0.08

sec.

 Wide QRS may indicate:

1. Ventricular contractions
2. Bundle branch block
3. Pre-excitation (Wolff-Parkinson White syndrome)

d) QT interval (measured from the beginning of Q to the end of T wave) represents both
ventricular depolarization and repolarization

• QTc is the QT interval corrected for the heart rate. QTc=QT (in seconds)/square root of
preceding RR interval (in seconds).
• See causes of long QT syndrome below.

Figure 9: Calculation of QT interval

 

5. Chamber Hypertrophy/Enlargement
 a) Right ventricular hypertrophy (RVH):

1. Voltage criteria (tall R in V1 and deep S in V6>95% for age) (see table below)
2. Right axis deviation
3. rSR' in V1 with a tall R' (> 10 mm)
4. qR pattern in V1;
5. Upright T wave in V1 > 1 week of age
o Newborns have upright T wave in V1
o T wave normally becomes inverted during the first week of life
o Upright T wave beyond the first week of life is a strong indicator of RVH
o T wave remains inverted in V1 throughout early childhood
o T wave becomes upright in V1 in late childhood and early adolescence and is
no longer diagnostic of RVH
o ~75% of adults have upright T wave in V1

b) Left ventricular hypertrophy (LVH): Criteria are not as well defined as RVH

1. Voltage criteria (tall R in V6 and deep S in V1);

2. Left axis deviation;
3. Strain pattern in left precordial leads (inverted T waves in V5 and V6)
6. Bundle Branch Block (delay in conduction in either the right or left bundle of His)

Incomplete right bundle branch block (iRBBB, RV conduction delay/ RV volume

overload)

1. Narrow QRS complexes

2. RSR' only in V1
3. Does not qualify for RVH criteria

Complete right bundle branch block

1. Wide QRS complexes in all leads preceded by P waves

2. rSR' in V1
3. Terminal slurring (widening of QRS) is positive in V1 and negative in V6

Complete left bundle branch block

1. Wide QRS complexes in all leads preceded by P waves

2. rSR' only in V6
3. Terminal slurring (widening of QRS) is positive in V6 and negative in V1
 Sumber : https://www.utmb.edu/pedi_ed/CoreV2/Cardiology/Cardiology4.html

3. Understand mechanism of cardiac arrhythmias.

A cardiac arrhythmia simply defined is a variation from the normal heart rate and/or rhythm
that is not physiologically justified. Recent years have witnessed important advances in our
understanding of the electrophysiologic mechanisms underlying the development of a variety
of cardiac arrhythmias. The mechanisms responsible for cardiac arrhythmias are generally
divided into 2 major categories: (1) enhanced or abnormal impulse formation (ie, focal
activity) and (2) conduction disturbances (ie, reentry) (Fig. 1).

Fig. 1
Classification of active cardiac arrhythmias.

ABNORMAL IMPULSE FORMATION

Normal Automaticity
Automaticity is the property of cardiac cells to generate spontaneous action potentials.
Spontaneous activity is the result of diastolic depolarization caused by a net inward current
during phase 4 of the action potential, which progressively brings the membrane potential to
threshold. The sinoatrial (SA) node normally displays the highest intrinsic rate. All other
pacemakers are referred to as subsidiary or latent pacemakers because they take over the
function of initiating excitation of the heart only when the SA node is unable to generate
impulses or when these impulses fail to propagate.

The Voltage and Calcium Clocks

The terms sarcolemma voltage or Ca clocks have been used by Maltsev and colleagues1 and
Lakatta2 to describe the mechanisms of SA node automaticity. The voltage clock refers to
voltage-sensitive membrane currents, such as the hyperpolarization-activated pacemaker
current (If).3 This current is also referred to as a “funny” current because, unlike most
voltage-sensitive currents, it is activated by hyperpolarization rather than depolarization. At
the end of the action potential, the If is activated and depolarizes the sarcolemmal
membrane.3 If is a mixed Na-K inward current modulated by the autonomic nervous system
through cAMP. The depolarization activates ICa,L, which provides Ca to activate the cardiac
ryanodine receptor (RyR2). The activation of RyR2 initiates sarcoplasmic reticulum (SR) Ca
release (Ca-induced Ca release), leading to contraction of the heart, a process known as EC
coupling. Intracellular Ca (Cai) is then pumped back into SR by the SR Ca-ATPase
(SERCA2a) and completes this Ca cycle. In addition to If, multiple time- and voltage-
dependent ionic currents have been identified in cardiac pacemaker cells, which contribute to
diastolic depolarization. These currents include (but are not limited to) ICa-L, ICa-T, IST, and
various types of delayed rectifier K currents.2 Many of these membrane currents are known to
respond to β-adrenergic stimulation. All these membrane ionic currents contribute to the
regulation of SA node automaticity by altering membrane potential.
Another important ionic current capable of depolarizing the cell is the sodium-calcium
exchanger current (INCx). In its forward mode, INCx exchanges 3 extracellular Na+ with 1
intracellular Ca2+, resulting in a net intracellular charge gain. This electrogenic current is
active during late phase 3 and phase 4 because the Cai decline outlasts the SA node action
potential duration. Recent studies showed that INCx may participate in normal pacemaker
activity.4 The sequence of events includes spontaneous rhythmic SR Ca release, Cai elevation,
the activation of INCx, and membrane depolarization. This process is highly regulated by
cAMP and the autonomic nervous system.2 These studies suggest that sympathetic
stimulation accelerates heart rate by phosphorylation of proteins that regulate Cai balance and
spontaneous SR Ca cycling. These proteins include phospholamban (PLB, an SR membrane
protein regulator of SERCA2a), L-type Ca channels, and RyR2. Phosphorylation of these
proteins controls the phase and extent of subsarcolemmal SR Ca releases.

Subsidiary Pacemakers
In addition to the SA node, the atrioventicular (AV) node and Purkinje system are also
capable of generating automatic activity. The contribution of If and IK differs in SA node/AV
nodes and Purkinje fiber because of the different potential ranges of these two pacemaker
types (ie, −70 to −35 mV and −90 to −65 mV, respectively). The contribution of other
voltage-dependent currents can also differ among the different cardiac cell types. Whether or
not the Ca clock plays a role in pacemaking of AV node and Purkinje cells remains unclear.
SA nodal cells possess the fastest intrinsic rates, making them the primary pacemakers in the
normal heart. When impulse generation or conduction in the SA node is impaired, latent or
subsidiary pacemakers within the atria or ventricles take control of pacing the heart. The
intrinsically slower rates of these latent pacemakers generally result in bradycardia. Both
atrial and AV junctional subsidiary pacemakers are under autonomic control, with the
sympathetic system increasing and parasympathetic system slowing the pacing rate. Although
acetylcholine produces little in the way of a direct effect, it can significantly reduce Purkinje
automaticity by means of the inhibition of the sympathetic influence, a phenomenon
termed accentuated antagonism.5 Simultaneous recording of cardiac sympathetic and
parasympathetic activity in ambulatory dogs confirmed that sympathetic activation followed
by vagal activation may be associated with significant bradycardia.6,7
Go to:

AUTOMATICITY AS A MECHANISM OF CARDIAC ARRHYTHMIAS

Abnormal automaticity includes both reduced automaticity, which causes bradycardia, and
increased automaticity, which causes tachycardia. Arrhythmias caused by abnormal
automaticity can result from diverse mechanisms (see Fig. 1). Alterations in sinus rate can be
accompanied by shifts of the origin of the dominant pacemaker within the sinus node or to
subsidiary pacemaker sites elsewhere in the atria. Impulse conduction out of the SA mode
can be impaired or blocked as a result of disease or increased vagal activity leading to
development of bradycardia. AV junctional rhythms occur when AV junctional pacemakers
located either in the AV node or in the His bundle accelerate to exceed the rate of SA node,
or when the SA nodal activation rate was too slow to suppress the AV junctional pacemaker.
Bradycardia can occur in structurally normal hearts because of genetic mutations that result
in abnormalities of either membrane clock or Ca clock mechanisms of automaticity. One
example is the mutation of hyperpolarization-activated nucleotide-gated channel (HCN4),
which is part of the channels that carry If. Mutations of the HCN4 may cause familial
bradycardia as well.8,9

Secondary SA Node Dysfunction

Common diseases, such as heart failure and atrial fibrillation, may be associated with
significant SA node dysfunction. Malfunction of both membrane voltage and Ca clocks might
be associated with both of these common diseases. Zicha and colleagues10 reported that
down-regulation of HCN4 expression contributes to heart failure-induced sinus node
dysfunction. An A450 V missense loss of function mutation in HCN4 has recently been
shown to underlie familial sinus bradycardia in several unrelated probands of Moroccan
Jewish descent.9,11–13

Enhanced Automaticity
Atrial and ventricular myocardial cells do not display spontaneous diastolic depolarization or
automaticity under normal conditions, but can develop these characteristics when
depolarized, resulting in the development of repetitive impulse initiation, a phenomenon
termed depolarization-induced automaticity.14 The membrane potential at which abnormal
automaticity develops ranges between −70 and −30 mV. The rate of abnormal automaticity is
substantially higher than that of normal automaticity and is a sensitive function of resting
membrane potential (ie, the more depolarized resting potential the faster the rate). Similar to
normal automaticity, abnormal automaticity is enhanced by β-adrenergic agonists and by
reduction of external potassium.
Depolarization of membrane potential associated with disease states is most commonly a
result of (1) an increase in extracellular potassium, which reduces the reversal potential
for IK1, the outward current that largely determines the resting membrane or maximum
diastolic potential; (2) a reduced number of IK1 channels; (3) a reduced ability of the
IK1 channel to conduct potassium ions; or (4) electrotonic influence of neighboring cells in the
depolarized zone. Because the conductance of IK1 channels is sensitive to extra-cellular
potassium concentration, hypokalemia can lead to major reduction in IK1, leading to
depolarization and the development of enhanced or abnormal automaticity, particularly in
Purkinje pacemakers. A reduction in IK1 can also occur secondary to a mutation in KCNJ2,
the gene that encodes for this channel, leading to increased automaticity and extrasystolic
activity presumably arising from the Purkinje system.15,16 Loss of function KCNJ2 mutation
gives rise to Andersen-Tawil syndrome, which is characterized among other things by a
marked increase in extrasystolic activity.17–20

Overdrive Suppression of Automaticity

Automatic activity of most pacemakers within the heart is inhibited when they are overdrive
paced,21 owing to a mechanism termed overdrive suppression. Under normal conditions, all
subsidiary pacemakers are overdrive-suppressed by SA nodal activity. A possible mechanism
of overdrive suppression is intracellular accumulation of Na leading to enhanced activity of
the sodium pump (sodium-potassium adenosine triphosphatase [Na+-K+ ATPase]), which
generates a hyperpolarizing electrogenic current that opposes phase 4 depolarization.22 The
faster the overdrive rate or the longer the duration of overdrive, the greater the enhancement
of sodium pump activity, so that the period of quiescence after cessation of overdrive is
directly related to the rate and duration of overdrive.

Parasystole and Modulated Parasystole

Latent pacemakers throughout the heart are generally reset by the propagating wavefront
initiated by the dominant pacemaker. An exception to this rule occurs when the pacemaking
tissue is protected from the impulse of sinus nodal origin. A region of entrance block arises
when cells exhibiting automaticity are surrounded by ischemic, infarcted, or otherwise
compromised cardiac tissues that prevent the propagating wave from invading the focus, but
which permit the spontaneous beat generated within the automatic focus to exit and activate
the rest of the myocardium. A pacemaker region exhibiting entrance block, and exit
conduction is referred to as a parasystolic focus. The ectopic activity generated by a
parasystolic focus is characterized by premature ventricular complexes with variable coupling
intervals, fusion beats, and inter-ectopic intervals that are multiples of a common
denominator. This rhythm is relatively rare and is usually considered benign, although a
premature ventricular activation of parasystolic origin can induce malignant ventricular
rhythms in the ischemic myocardium or in the presence of a suitable myocardial substrate.
Modulated parasystole, a variant of classical parasystole, was described by Jalife and
colleagues.23,24 This variant of the arrhythmia results from incomplete entrance block of the
parasystolic focus. Electrotonic influences arriving early in the pacemaker cycle delayed and
those arriving late in the cycle accelerated the firing of the parasystolic pacemaker, so that
ventricular activity could entrain the partially protected pacemaker. As a consequence, at
select heart rate, extrasystolic activity generated by the entrained parasystolic pacemaker can
mimic reentry, generating extrasystolic activity with fixed coupling.23–27
Go to:

AFTERDEPOLARIZATION AND TRIGGERED ACTIVITY

Depolarizations that attend or follow the cardiac action potential and depend on preceding
transmembrane activity for their manifestation are referred to as afterdepolarizations (Fig. 2).
Two subclasses are traditionally recognized: (1) early, and (2) delayed. Early
afterdepolarization (EAD) interrupts or retards repolarization during phase 2 and/or phase 3
of the cardiac action potential, whereas delayed afterdepolarization (DAD) occurs after full
repolarization. When EAD or DAD amplitude suffices to bring the membrane to its threshold
potential, a spontaneous action potential referred to as a triggered response is the result
(see Fig. 2). These triggered events give rise to extrasystoles, which can precipitate
tachyarrhythmias.

Fig. 2
Examples of early afterdepolarization (EAD) (A), delayed afterdepolarization (DAD) (B), and
late phase 3 EAD (C). (Modified from Burashnikov A, Antzelevitch C. Late-phase 3 EAD. A
unique mechanism contributing to initiation of atrial fibrillation. Pacing Clin Electrophysiol
2006;29:290–5; with permission.)

Early Afterdepolarizations and Triggered Activity

EADs are typically observed in cardiac tissues exposed to injury, altered electrolytes,
hypoxia, acidosis, catecholamines, and pharmacologic agents, including antiarrhythmic
drugs. Ventricular hypertrophy and heart failure also predispose to the development of
EADs.28 EAD characteristics vary as a function of animal species, tissue or cell type, and the
method by which the EAD is elicited. Although specific mechanisms of EAD induction can
differ, a critical prolongation of repolarization accompanies most, but not all, EADs. Drugs
that inhibit potassium currents or which augment inward currents predispose to the
development of EADs.29 Phase 2 and phase 3 EADs sometimes appear in the same
preparation.
EAD-induced triggered activity is sensitive to stimulation rate. Antiarrhythmic drugs with
class III action generally induce EAD activity at slow stimulation rates.14 In contrast, β-
adrenergic agonist–induced EADs are fast rate-dependent.30 In the presence of rapidly
activating delayed rectifier current (rapid outward potassium current [IKr]) blockers, β-
adrenergic agonists, and/or acceleration from an initially slow rate transiently facilitate the
induction of EAD activity in ventricular M cells, but not in epicardium or endocardium and
rarely in Purkinje fibers.31

Cellular Origin of Early Afterdepolarizations

EADs develop more commonly in midmyocardial M cells and Purkinje fibers than in
epicardial or endocardial cells when exposed to action potential duration (APD)-prolonging
agents. This is because of the presence of a weaker IKs and stronger late INa in M
cells.32,33 Block of IKs with chromanol 293B permits the induction of EADs in canine
epicardial and endocardial tissues in response to IKr blockers such as E-4031 or sotalol.34 The
predisposition of cardiac cells to the development of EADs depends principally on the
reduced availability of IKr and IKs as occurs in many forms of cardiomyopathy. Under these
conditions, EADs can appear in any part of the ventricular myocardium.35

Ionic Mechanisms Responsible for the EAD

EADs develop when the balance of current active during phase 2 and/or 3 of the action
potential shifts in the inward direction. If the change in current-voltage relation results in a
region of net inward current during the plateau range of membrane potentials, it leads to a
depolarization or EAD. Most pharmacologic interventions or pathophysiological conditions
associated with EADs can be categorized as acting predominantly through 1 of 4 different
mechanisms: (1) A reduction of repolarizing potassium currents (IKr, class IA and III
antiarrhythmic agents; IKs, chromanol 293B or IK1); (2) an increase in the availability of
calcium current (Bay K 8644, catecholamines); (3) an increase in the sodium-calcium
exchange current (INCx) caused by augmentation of Cai activity or upregulation of the INCx; and
(4) an increase in late sodium current (late INa) (aconitine, anthopleurin-A, and ATX-II).
Combinations of these interventions (ie, calcium loading and IKr reduction) or
pathophysiological states can act synergistically to facilitate the development of EADs.

Delayed Afterdepolarization-Induced Triggered Activity

DADs and DAD-induced triggered activity are observed under conditions that augment
intracellular calcium, [Ca2+]i, such as after exposure to toxic levels of cardiac glycosides
(digitalis)36–38 or catecholamines.30,39,40 This activity is also manifest in hypertrophied and
failing hearts41,42 as well as in Purkinje fibers surviving myocardial infarction.43 In contrast to
EADs, DADs are always induced at relatively rapid rates.

Role of Delayed Afterdepolarization-Induced Triggered Activity in the Development of

Cardiac Arrhythmias
An example of DAD-induced arrhythmia is the catecholaminergic polymorphic ventricular
tachycardia (CPVT), which may be caused by the mutation of either the type 2 ryanodine
receptor (RyR2) or the calsequestrin (CSQ2).44 The principal mechanism underlying these
arrhythmias is the “leaky” ryanodine receptor, which is aggravated during catecholamine
stimulation. A typical clinical phenotype of CPVT is bidirectional ventricular tachycardia,
which is also seen in digitalis toxicity. Wehrens and colleagues45 demonstrated that
heterozygous mutation of FKBP12.6 leads to leaky RyR2 and exercise-induced VT and VF,
simulating the human CPVT phenotype. RyR2 stabilization with a derivative of 1,4-
benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the
closed state of RyR2 and prevented the Ca leak that triggers arrhythmias. Other studies
indicate that delayed afterdepolarization-induced extrasystoles serve to trigger
catecholamine-induced VT/VF, but that the epicardial origin of these ectopic beats increases
transmural dispersion of repolarization, thus providing the substrate for the development of
reentrant tachyarrhythmias, which underlie the rapid polymorphic VT/VF.46 Heart failure is
associated with structural and electrophysiological remodeling, leading to tissue
heterogeneity that enhances arrhythmogenesis and the propensity of sudden cardiac death.47

Late Phase 3 Early Afterdepolarizations and Their Role in the Initiation of Fibrillation
In 2003, Burashnikov and Antzelevitch48,49 described a novel mechanism giving rise to
triggered activity, termed “late phase 3 EAD,” which combines properties of both EAD and
DAD, but has its own unique character (see Fig. 2). Late phase 3 EAD-induced triggered
extrasystoles represent a new concept of arrhythmogenesis in which abbreviated
repolarization permits “normal SR calcium release” to induce an EAD-mediated closely
coupled triggered response, particularly under conditions permitting intracellular calcium
loading.48,49 These EADs are distinguished by the fact that they interrupt the final phase of
repolarization of the action potential (late phase 3). In contrast to previously described DAD
or Cai-dependent EAD, it is normal, not spontaneous SR calcium release that is responsible
for the generation of the EAD. Two principal conditions are required for the appearance of
late phase 3 EAD: an APD abbreviation and a strong SR calcium release.48 Such conditions
may occur when both parasympathetic and sympathetic influences are combined.
Simultaneous sympathovagal activation is also known to be the primary trigger of
paroxysmal atrial tachycardia and AF episodes in dogs with intermittent rapid pacing.6
Late phase 3 EAD-induced extrasystoles have been shown to initiate AF in canine atria,
particularly following spontaneous termination of the arrhythmia (IRAF, immediate
reinduction of AF).48 The appearance of late phase 3 EAD immediately following termination
of AF or rapid pacing has been reported by in the canine atria in vivo50 and pulmonary veins
in vitro.51 In addition to the atrial arrhythmias, late phase 3 EAD may also be responsible for
the development recurrent VF in failing hearts.
Sumber : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164530/

4. Understand clinical aspects of cardiac arrhythmias.

Heart Rhythms on ECG

The heart’s electrical system triggers the heartbeat. Each beat of the heart is represented on
the electrocardiogram (EKG or ECG) by a wave arm.

The normal heart rhythm (normal sinus rhythm) shows the electrical activity in the heart is
following the normal pathway. The rhythm is regular and the node is normal (about 50 to 100
beats per minute).
Tachycardia: fast heart rhythm (greater than 100 beats per minute)

Bradycardia: slow heart rhythm (less than 60 beats per minute)

The Heart’s Electrical System

The atria (the heart’s upper chambers) and ventricles (the heart’s lower chambers) work
together, alternately contracting and relaxing to pump blood through the heart. The electrical
system of the heart is the power source that makes this possible. Here’s what happens during
a normal heartbeat:

Irregular heart rhythms can also occur in normal, healthy hearts. Arrhythmias can also be
caused by certain substances or medications, such as caffeine, nicotine, alcohol, cocaine,
inhaled aerosols, diet pills, and cough and cold remedies. Emotional states such as shock,
fright or stress can also cause irregular heart rhythms.

Arrhythmias that are recurrent or related to an underlying heart condition are more
concerning and should always be evaluated by a doctor.

In most cases, treating the underlying condition will take care of the arrhythmia. If not, many
medications and procedures are available to eliminate or control the abnormal heart rhythm.

What are the types of arrhythmias?

 Tachycardia: A fast heart rhythm with a rate of more than 100 beats per minute.
 Bradycardia: A slow heart rhythm with a rate below 60 beats per minute.
 Supraventricular arrhythmias: Arrhythmias that begin in the atria (the heart’s
upper chambers). “Supra” means above; “ventricular” refers to the lower chambers
of the heart, or ventricles.
 Ventricular arrhythmias: Arrhythmias that begin in the ventricles (the heart’s lower
chambers).
 Bradyarrhythmias: Slow heart rhythms that may be caused by disease in the heart’s
conduction system, such as the sinoatrial (SA) node, atrioventricular (AV) node or
His-Purkinje network.

Types of Supraventricular Arrhythmias

Supraventricular arrhythmias begin in the atria

Types of supraventricular arrhythmias include:

Premature atrial contractions (PACs)

Early, extra heartbeats that originate in the atria.

Paroxysmal supraventricular tachycardia (PSVT)

A rapid but regular heart rhythm that comes from the atria. This type of arrhythmia begins
and ends suddenly.
Accessory pathway tachycardias (bypass tract tachycardias)

A fast heart rhythm caused by an extra, abnormal electrical pathway or connection between
the atria and ventricles. The impulses travel through the extra pathways as well as the usual
route. This allows the impulses to travel around the heart very quickly, causing the heart to
beat unusually fast (example: Wolff- Parkinson-White syndrome).

AV nodal re-entrant tachycardia (AVNRT)

A fast heart rhythm caused by the presence of more than one pathway through the
atrioventricular (AV) node.

Atrial tachycardia

A rapid heart rhythm that originates in the atria.

Atrial fibrillation

A very common irregular heart rhythm. Many impulses begin and spread through the atria,
competing for a chance to travel through the AV node. The resulting rhythm is disorganized,
rapid and irregular. Because the impulses are traveling through the atria in a disorderly
fashion, there is a loss of coordinated atrial contraction.

Atrial flutter

An atrial arrhythmia caused by one or more rapid circuits in the atrium. Atrial flutter is
usually more organized and regular than atrial fibrillation.

Types of Ventricular Arrhythmias

A ventricular arrhythmia begins in the heart’s ventricles.

Types of ventricular arrhythmias include:

Premature ventricular contractions (PVCs)

Early, extra heartbeats that originate in the ventricles. Most of the time, PVCs don’t cause
any symptoms or require treatment. This type of arrhythmia is common and can be related to
stress, too much caffeine or nicotine, or exercise. They can be also be caused by heart disease
or electrolyte imbalance. People who have several PVCs and/or symptoms associated with
them should be evaluated by a cardiologist (heart doctor).

Ventricular tachycardia (V-tach)

A rapid heartbeat that originates in the ventricles. The rapid rhythm keeps the heart from
adequately filling with blood, and less blood is able to pump through the body. V-tach can be
serious, especially in people with heart disease, and may be associated with more symptoms
than other types of arrhythmia. A cardiologist should evaluate this condition.

Ventricular fibrillation (V-fib)

An erratic, disorganized firing of impulses from the ventricles. The ventricles quiver and
cannot generate an effective contraction, which results in a lack of blood being delivered to
the body. This is a medical emergency that must be treated with cardiopulmonary
resuscitation (CPR) and defibrillation (delivery of an energy shock to the heart muscle to
restore a normal rhythm) as soon as possible.

Long QT

The QT interval is the area on the ECG that represents the time it takes for the heart muscle
to contract and then recover, or for the electrical impulse to fire and then recharge. When the
QT interval is longer than normal, it increases the risk for “torsade de pointes,” a life-
threatening form of ventricular tachycardia.

Types of Bradyarrhythmias

A bradyarrhythmia is a slow heart rhythm that is usually caused by disease in the heart’s

conduction system. Types of bradyarrhythmias include:

Sinus node dysfunction

Slow heart rhythms due to an abnormal SA node.

Heart block

A delay or complete block of the electrical impulse as it travels from the sinus node to the
ventricles. The level of the block or delay may occur in the AV node or His-Purkinje system.
The heartbeat may be irregular and slow.

SYMPTOMS AND CAUSES

What are the symptoms of an arrhythmia?

An arrhythmia may be “silent” and not cause any symptoms. A doctor can detect an irregular
heartbeat during an examination by taking your pulse, listening to your heart or by
performing diagnostic tests. If symptoms occur, they may include:

 Palpitations: A feeling of skipped heartbeats, fluttering, "flip-flops" or feeling that the

heart is "running away"
 Pounding in the chest
 Dizziness or feeling lightheaded
 Shortness of breath
 Chest discomfort
 Weakness or fatigue (feeling very tired)

What causes arrhythmias?

Arrhythmias can be caused by:

 Coronary artery disease

  High blood pressure
 Changes in the heart muscle (cardiomyopathy)
 Valve disorders
 Electrolyte imbalances in the blood, such as sodium or potassium
 Injury from a heart attack
 The healing process after heart surgery
 Other medical conditions

DIAGNOSIS AND TESTS

How is an arrhythmia diagnosed?

If you have symptoms of an arrhythmia, you should make an appointment with a cardiologist.
You may want to see an electrophysiologist — a cardiologist who has additional specialized
training in the diagnosis and treatment of heart rhythm disorders.After evaluating your
symptoms and performing a physical examination, the cardiologist may perform a variety of
diagnostic tests to help confirm the presence of an arrhythmia and indicate its causes.Some
tests that may be done to confirm the presence of an irregular heart rhythm include:

 Electrocardiogram (ECG or EKG): A picture of the electrical impulses traveling

through the heart muscle. An ECG is recorded on graph paper, through the use of
electrodes (small, sticky patches) that are attached to your skin on the chest, arms and
legs.
 Ambulatory monitors, such as:
 Stress test: A test used to record arrhythmias that start or are worsened with exercise.
This test also may be helpful in determining if there is underlying heart disease or
coronary artery disease associated with an arrhythmia.
 Echocardiogram: A type of ultrasound used to provide a view of the heart to
determine if there is heart muscle or valve disease that may be causing an arrhythmia.
This test may be performed at rest or with activity.
 Cardiac catheterization: Using a local anesthetic, a catheter (small, hollow, flexible
tube) is inserted into a blood vessel and guided to the heart with the help of an X-ray
machine. A contrast dye is injected through the catheter so X-ray movies of your
coronary arteries, heart chambers and valves may be taken. This test helps your doctor
determine if the cause of an arrhythmia is coronary artery disease. This test also
provides information about how well your heart muscle and valves are working.
 Electrophysiology study (EPS): A special heart catheterization that evaluates your
heart’s electrical system. Catheters are inserted into your heart to record the electrical
activity. The EPS is used to find the cause of the abnormal rhythm and determine the
best treatment for you. During the test, the arrhythmia can be safely reproduced and
terminated.
 Tilt table test (also called a passive head-up tilt test or head upright tilt test): Records
your blood pressure and heart rate on a minute-by-minute basis while the table is
tilted in a head-up position at different levels. The test results may be used to evaluate
heart rhythm, blood pressure and sometimes other measurements as you change
position.

MANAGEMENT AND TREATMENT

How is an arrhythmia treated?

Treatment depends on the type and severity of your arrhythmia. In some cases, no treatment
is necessary. Treatment options include medications, lifestyle changes, invasive therapies,
electrical devices or surgery.

Medications

Antiarrhythmic drugs are medications used to convert the arrhythmia to a normal sinus
rhythm or to prevent an arrhythmia. Other medications may include heart rate-control drugs
and anticoagulant or antiplatelet drugs such as warfarin (a “blood thinner”) or aspirin, which
reduce your risk of stroke or developing blood clots.It is important that you know the names
of your medications, why they are prescribed, how often and at what times to take them, what
side effects may occur, and what medications you have previously taken for your arrhythmia.

 Common Medications for Arrythmias

Lifestyle changes

Arrhythmias may be related to certain lifestyle factors. The following tips can help limit the
occurrence of arrhythmias:

 If you smoke, stop.

 Limit your intake of alcohol.
 Limit or stop using caffeine. Some people are sensitive to caffeine and may notice
more symptoms when using caffeinated products, such as tea, coffee, colas and some
over-the- counter medications.
 Avoid using stimulants. Beware of stimulants used in cough and cold medications and
herbal or nutritional supplements. Some of these substances contain ingredients that
cause irregular heart rhythms. Read the label and ask your doctor or pharmacist which
medication is best for you.
 Your family may also want to be involved in your care by learning to recognize your
symptoms and how to start CPR if needed.
 If you notice that your irregular heart rhythm occurs more often with certain activities,
you should avoid them.

Invasive therapies

Electrical cardioversion and catheter ablation are invasive therapies used to treat or eliminate
irregular heart rhythms. Your doctor will determine the best treatment for you and discuss the
benefits and risks of these therapies with you.

 Electrical cardioversion Patients with persistent arrhythmias, such as atrial

fibrillation, may not be able to achieve a normal heart rhythm with drug therapy
alone. Electrical cardioversion delivers an electrical shock to your chest wall, which
synchronizes the heart and allows the normal rhythm to restart. This procedure is done
after you receive short-acting anesthesia.
 Catheter ablation: During ablation, energy is delivered through a catheter to tiny
areas of the heart muscle. This energy can either “disconnect” the pathway of the
 abnormal rhythm, block the abnormal pulses and promote normal conduction of
impulses, or disconnect the electrical pathway between the atria and the ventricles.
o Pulmonary vein isolation: In patients with frequent, paroxysmal or persistent
atrial fibrillation, isolation of the pulmonary veins is a procedure that uses
special catheters to render bands of vein tissue, thought to cause atrial
fibrillation, dysfunctional. The goal is to isolate, rather than ablate, the foci
responsible for triggering atrial fibrillation through a circumferential
conduction block.
 Electrical devices

 Permanent pacemaker: A device that sends small electrical impulses to the heart
muscle to maintain a normal heart rate. The pacemaker has a pulse generator (which
houses a battery and a tiny computer) and leads (wires) that send impulses from the
pulse generator to your heart muscle, as well as sense the heart’s electrical activity.
Pacemakers are mostly used to prevent the heart from beating too slowly. Newer
pacemakers have many sophisticated features that are designed to help manage
arrhythmias, optimize heart rate-related functions and improve synchronization.
 Implantable cardioverter-defibrillator (ICD): A sophisticated electronic device
used primarily to treat ventricular tachycardia and ventricular fibrillation — two life-
threatening abnormal heart rhythms. The ICD constantly monitors the heart rhythm.
When it detects a very fast, abnormal heart rhythm, it delivers energy to the heart
muscle to cause the heart to beat in a normal rhythm again.

There are several ways an ICD can restore a normal heart rhythm:

 Antitachycardia pacing (ATP): When the heart beats too fast, a series of small
electrical impulses are delivered to the heart muscle to restore a normal heart rate and
rhythm.
 Cardioversion: A low-energy shock is delivered at the same time as the heartbeat to
restore a normal heart rhythm.
 Defibrillation: When the heart is beating dangerously fast or irregularly, a higher
energy shock is delivered to the heart muscle to restore a normal rhythm.
 Antibrachycardia pacing: Many ICDs provide back-up pacing to prevent heart
rhythms that are too slow.

Heart surgery

Surgery may be needed to correct arrhythmias that can’t be controlled with medications or
nonsurgical treatment methods. Arrhythmia surgery may also be recommended if you need
surgery, such as valve surgery or bypass surgery, to correct other forms of heart disease. The
Maze and modified Maze procedures are two surgeries used to correct atrial fibrillation.Your
doctor will determine the best treatment for you and discuss these options with you, including
more information about surgical treatment if it is an appropriate treatment option.

Sumber : https://my.clevelandclinic.org/health/diseases/16749-arrhythmia

5. Define diagnosis tool in cardiovascular diseases.

Cardiovascular diseases are diagnosed using an array of laboratory tests and imaging studies.
The primary part of diagnosis is medical and family histories of the patient, risk factors,
physical examination and coordination of these findings with the results from tests and
procedures.

Some of the common tests used to diagnose cardiovascular diseases include:

Blood Tests

Laboratory tests are used to detect the risk factors for heart diseases. These include detection
of the fats, cholesterol and lipid components of blood including LDL, HDL, Triglycerides.

Blood sugar and Glycosylated hemoglobin is measured for detection of diabetes. C-reactive
protein (CRP) and other protein markers like Apolipoprotein A1 and B are used to detect
inflammation that may lead to heart diseases.

During a heart attack, heart muscle cells die and release proteins into the bloodstream. Blood
tests can measure the amount of these proteins in the bloodstream. High levels of these
proteins are a sign of a recent heart attack.

One of the markers of heart attack is the Cardiac Troponin-T. Other biomarkers include
fibrinogen and PAI-1, high levels of homocysteine, elevated asymmetric dimethylarginine
and elevated brain natriuretic peptide (also known as B-type) (BNP)

EKG/ECG  (Electrocardiogram)

This is a simple and a painless test that records the heart’s electrical activity. The patient is
strapped to the instrument with several patches or leads placed over his or her chest, wrists
and ankles. A small portable machine records the activities of the heart on a strip of graph
paper.
The test shows how fast the heart is beating and its rhythm. The strength and timing of the
electrical signals as they pass through the heart are also seen. An EKG/ECG can help detect a
heart attack, attacks of angina, arrhythmias etc.

Stress Testing
Related Stories

 Impact of dairy fats on cardiovascular disease

 Study to examine psychosocial factors associated with CVD risk among urban
African American adults
 Atherosclerosis found in more than 40% of adults in Sweden without known heart
disease

For this test, the patient is made to work hard e.g. run on a treadmill or exercise while the
leads of EKG/ECG are placed over their body. Those who cannot exercise are given pills to
raise their heart rate. The test detects the effects of the exercise on the heart.

In patients with atheroisclerosis and coronary heart diseases the arteries that are narrowed by
plaques cannot supply adequate blood to the heart muscles while it is beating faster. This may
lead to shortness of breath and chest pain. The EKG/ECG pattern, arrhythmias etc. also show
the possibility of a coronary artery disease.

Echocardiography

This test uses sound waves to create a moving picture of the heart. This is also a painless test
where a probe is rolled over the chest and the machine creates the image of the heart on the
monitor. This provides information on the shape, size, workings, valves and chambers of the
heart.

Echocardiography may also be combined with Doppler to show the areas of poor blood
supply to the heart. It shows the areas of the heart muscle that are not contracting normally,
and previous injury to the heart muscle.

Coronary Angiography and Cardiac Catheterization

This test is an invasive test. A dye is injected into the veins to reach the coronary arteries.
This is done via coronary catheterization. Thereafter detailed pictures of the blood vessels of
the heart are taken using special imaging methods. This is called coronary angiography.

Cardiac catheterization involves threading of a thin, flexible tube called a catheter via a blood
vessels in the arm, groin (upper thigh), or neck. The tube is inserted under imagin guidance
till it reaches the heart. Coronary angiography detects blockages in the large coronary
arteries.

Chest X Ray

This is a test that shows the shape and size of the heart lungs and major blood vessels. This is
a test seldom used in diagnosis of heart diseases as it does not provide added information
over echocardiography and other imaging studies.

Electron-Beam Computed Tomography or EBCT

EBCT helps to detect the calcium deposits or calcifications in the walls of the coronary
arteries. These are early markers of atherosclerosis and coronary heart disease. This is not a
routine test in coronary heart disease.

Cardiac MRI

Cardiac MRI (magnetic resonance imaging) that uses radio waves, magnets, and a computer
to create pictures of the heart. This gives a 3D image of the moving as well as still pictures of
the heart.

Sumber : https://www.news-medical.net/health/Cardiovascular-Disease-Diagnosis.aspx

6. Describe the pharmacodynamics aspect of anti-arrhythmia drugs.

Therapeutic Use and Rationale

The ultimate goal of antiarrhythmic drug therapy is to restore normal rhythm and conduction.
When it is not possible to revert to normal sinus rhythm, drugs may be used to prevent more
serious and possibly lethal arrhythmias from occurring. Antiarrhythmic drugs are used to:

 decrease or increase conduction velocity

 alter the excitability of cardiac cells by changing the duration of the effective
refractory period
 suppress abnormal automaticity
All antiarrhythmic drugs directly or indirectly alter membrane ion conductances, which in
turn alters the physical characteristics of cardiac action potentials. For example, some drugs
are used to block fast sodium channels. These channels determine how fast the membrane
depolarizes (phase 0) during an action potential. Since conduction velocity is related to how
fast the membrane depolarizes, sodium channel blockers reduce conduction velocity.
Decreasing conduction velocity can help to abolish tachyarrhythmias caused by reentry
circuits. Other types of antiarrhythmic drugs affect the duration of action potentials, and
especially the effective refractory period. By prolonging the effective refractory period,
reentry tachycardias can often be abolished. These drugs typically affect potassium channels
and delay repolarization of action potentials (phase 3). Drugs that block slow inward calcium
channels are used to reduce pacemaker firing rate by slowing the rate of rise of depolarizing
pacemaker potentials (phase 4 depolarization). These drugs also reduce conduction velocity
at the AV node, because those cells, like SA nodal cells, depend on the inward movement of
calcium ions to depolarize.

Because sympathetic activity can precipitate arrhythmias, drugs that block beta1-

adrenoceptors are used to inhibit sympathetic effects on the heart. Because beta-
adrenoceptors are coupled to ion channels through defined signal transduction pathways,
beta-blockers indirectly alter membrane ion conductance, particularly calcium and potassium
conductance.

In the case of AV block, drugs that block vagal influences (e.g., atropine, a muscarinic
receptor antagonist) are sometimes used. AV block can occur during beta-blocker treatment
and therefore simply removing a beta-blocker in patients being treated with such drugs may
normalize AV conduction.

Sometimes ventricular rate is excessively high because it is being driven by atrial flutter or
fibrillation. Because it is very important to reverse ventricular tachycardia, drugs are often
used to slow AV nodal conduction. Calcium channel blockers and beta-blockers are useful
for this indication. Digitalis, because of its ability to activate the vagus nerve
(parasympathomimetic effect), can also be used to reduce AV conduction velocity in an
attempt to normalize ventricular rate during atrial flutter or fibrillation.

Classes of Drugs Used to Treat Arrhythmias

Classes of drugs used in the treatment of arrhythmias are given below.  Clicking on the drug
class will link you to the page describing the pharmacology of that drug class and specific
drugs. Please note that many of the drugs comprising the first five listed classes have
considerable overlap in their pharmacologic properties.

Antiarrhythmic drug classes:

 Class I - Sodium-channel blockers
 Class II - Beta-blockers
 Class III - Potassium-channel blockers
 Class IV - Calcium-channel blockers
 Miscellaneous - adenosine
- electrolyte supplement (magnesium and potassium salts)
- digitalis compounds (cardiac glycosides)
- atropine (muscarinic receptor antagonist)

Sumber : https://www.cvpharmacology.com/antiarrhy/antiarrhythmic